Marian Vincenzi, Flavia Anna Mercurio and Marilisa Leone* Pages 450 - 476 ( 27 )
Background: The sterile alpha motif (Sam) domain is a small helical protein module, able to undergo homo- and hetero-oligomerization, as well as polymerization, thus forming different types of protein architectures. A few Sam domains are involved in pathological processes and consequently, they represent valuable targets for the development of new potential therapeutic routes. This study intends to collect state-of-the-art knowledge on the different modes by which Sam domains can favor disease onset and progression.
Methods: This review was build up by searching throughout the literature, for: a) the structural properties of Sam domains, b) interactions mediated by a Sam module, c) presence of a Sam domain in proteins relevant for a specific disease.
Results: Sam domains appear crucial in many diseases including cancer, renal disorders, cataracts. Often pathologies are linked to mutations directly positioned in the Sam domains that alter their stability and/or affect interactions that are crucial for proper protein functions. In only a few diseases, the Sam motif plays a kind of "side role" and cooperates to the pathological event by enhancing the action of a different protein domain.
Conclusion: Considering the many roles of the Sam domain into a significant variety of diseases, more efforts and novel drug discovery campaigns need to be engaged to find out small molecules and/or peptides targeting Sam domains. Such compounds may represent the pillars on which to build novel therapeutic strategies to cure different pathologies.
Sam domains, drug discovery, structural biology, protein-protein interactions, diseases, therapeutic routes
Institute of Biostructures and Bioimaging, National Research Council (CNR), Via Mezzocannone 16, 80134 Naples, Institute of Biostructures and Bioimaging, National Research Council (CNR), Via Mezzocannone 16, 80134 Naples, Institute of Biostructures and Bioimaging, National Research Council (CNR), Via Mezzocannone 16, 80134 Naples